OBJECTIVE:
To profile adult patients dying of tuberculosis in the city of São Paulo
with respect to biological, environmental and institutional factors.METHODS: Descriptive study covering all tuberculosis deaths (N=416)
among individuals aged over 15 years in 2002. Data were obtained from hospital
records, the local Mortality Information System, Coroner's Service, and tuberculosis
Surveillance System. The estimates of relative risk and 95% confidence intervals
(95% CI) were based on the reference group, i.e., females aged 15 to 29 years,
originally from the State of São Paulo (Brazil). A comparative analysis
was conducted using Pearson's chi-square test and Fisher's exact test for categorical
variables and Kruskal-Wallis test for continuous variables.RESULTS: Of all tuberculosis deaths identified, 78% had pulmonary form.
Tuberculosis diagnosis was made after death in 30% and in primary health care
units in 14%. Of them, 44% had not started treatment; 49% were not notified;
and 76% were men. The median age was 51 years; 52% had up to four years of schooling;
4% were probably living in the streets. Mortality rate increased with age; it
was 5.0/100,000 for the entire city, ranging between zero to 35 according to
the district. Previous treatment was reported for 82 out of 232 patients, and
of them, 41 defaulted treatment. Diabetes (16%), chronic obstructive pulmonary
disease (19%), HIV infection (11%), smoking (71%), and alcohol abuse (64%) were
also reported.CONCLUSIONS: Adult males over 50, migrants and living in lower Human
Development Index districts were more likely to die of tuberculosis. Low schooling
and comorbidities are relevant characteristics. Low involvement of primary care
units in tuberculosis diagnosis and high underreporting of cases were also seen.

Brazil ranks among
the countries with the highest rates of tuberculosis (TB) morbidity and mortality
with around 85,000 new TB cases and 6,000 deaths every year.6 From
1980 to 1995, the proportion of deaths associated to TB compared to total deaths
due to infectious diseases (International Classification of Diseases - 10th
Revision [ICD-10]; Chapter I) increased from 10.1% to 15.5%.13
This data point to the high endemicity of TB in Brazil and evidence this disease
trend which contrast with the marked decline that seen for most other infectious
diseases in the last 20 years.4,a

For the city of
São Paulo, TB morbidity and mortality rates are close to mean rates reported
nationwide; however, they are higher than that seen in the interior of the State
of São Paulob (Galesi
1998). In 2000, the city of São Paulo had an incidence rate of 65 per
100,000 inhabitants, 60% of them new bacillary TB cases and a mortality rate
of 5.7 per 100,000. Incidence rates varied widely by districts ranging from
18.7 to 261.1 per 100,000, while mortality rates were nil in some districts
and as high as 20.9 per 100,000 in the poorest districts.c

Data available
on TB control activities in the city of São Paulo are consistent with
the seriousness of this endemic, i.e., in 2000, there were about 70% of cure,
20% of treatment default and 13% of case-fatality rate.c

The objective of
the present study was to profile adult patients dying of TB in the city of São
Paulo with respect to biological, environmental and institutional factors.

METHODS

The city of São
Paulo has approximately 10 million inhabitants and is characterized by a wide-ranging
Human Development Index (HDI), from 0.245 in poorer districts to 0.811 in well-off
ones.d

This is a descriptive
study including all patients, both males and females, aged 15 years or more,
living in the city of São Paulo who progressed to death due to any clinical
form of TB as a main cause of death (codes A15 to A19, ICD 10) between January
and December 2002.

The following variables
were studied: gender; age; race/ethnicity; origin; marital status; schooling;
district of residence; place of death; clinical form; type of service where
the diagnosis was made; criteria for diagnosis; time between symptom onset and
diagnosis; treatment duration of TB episode progressing to death; length of
hospital stay before death; type of treatment; past history of TB; outcome of
prior treatment (cure, default), comorbidities and other conditions (diabetes,
cancer, chronic obstructive pulmonary disease, TB/HIV co-infection, alcohol
abuse, smoking) and case reporting to TB Surveillance System.

Data was obtained
from the following information sources: Mortality Information System of the
City of São Paulo (PROAIM) for identification of TB deaths and collection
of data from death certificates; hospital records where TB deaths occurred;
Coroners Service of the State of São Paulo for anatomopathology (macroscopic)
examination results; TB Surveillance System, Center for Disease Control of the
City of São Paulo (CCD) for ascertainment of cases reported and data
collection; Brazilian Institute of Geography and Statistics (IBGE) for population
data used in estimates of mortality rates. Data obtained from TB Surveillance
System were updated as for September 2003.

A pre-coded form
was used for data collection from all the different sources. Data were double
entered and a database was created using EpiInfo software program, version 6.4.

Mortality rates
by gender, age group, district of residence and origin were calculated using
the number of deaths identified in the study in the numerator and population
aged 15 years or more estimated as for July 1st, 2002 in the denominator.
Estimates of relative risks and 95% confidence intervals (95% CI) were based
on female gender, age group between 15 to 29 years and originally from the State
of São Paulo as reference.

TabWin program
was applied for mapping mortality rates by city district. In the comparative
analysis, Pearson's chi-square test and Fisher's exact test were used for categorical
variables and Kruskal-Wallis test for continuous variables. All estimates were
performed using EpiInfo version 6.4 and SPSS software programs version 14.

The study was approved
by the Research Ethics Committee of Universidade de São Paulo School
of Medicine.

RESULTS

A total of 416
deaths due to TB as primary cause were identified in 2002. The most common clinical
forms were pulmonary (77.9%) and disseminated (17.5%). Of them, 44.1% were untreated
cases, 51.1% received regimen 1 (isoniazid, rifampicin and pyrazinamide) and
4.8% regimen 1R (isoniazid, rifampicin, pyrazinamide, and ethambutol); 20.2%
and 38.5% were treated for at least one week or up to one month, respectively,
before dying.

Among those treated
patients, 82/232 (35.3%) had past history of TB, of which 50% had defaulted
prior treatment and 34/82 (41.5%) had TB in the last two years. For 30.4% TB
diagnosis was made only after death.

Of all deaths identified,
86.0%, 11.1% and 2.9% took place in hospitals, at home and in a public road,
respectively. Of those who died in a hospital, 20.1% and 43.1% died within the
first 24 and 72 hours after admission, respectively. Criteria for diagnostic
confirmation were: bacteriological examination in 31.8%, anatomopathology (macroscopic)
examination in 38.9%, clinical-radiology evaluation in 27.2% and histopathology
examination in 2.1%.

Of 416 deaths,
19.5% received home visits to search for TB cases among household contacts.
Of those cases not reported (n=206; 49.5%), 187 were untreated. Address information
was missing for 15 patients (3.6%), and personal identification was also missing
for six of them and none of these cases had been reported, suggesting they were
homeless.

Median age was
51 years (16 to 98 years), 53 years in women (17 to 98 years) and 50 in men
(16 to 93 years) (p> 0.05); and 75.5% of deaths were in males. According
to death certificate information, 54.7% were White, 27.2% were mixed; 16.1%
were Black, and 2.0% were Asian.

Of 202 deaths with
schooling information, 51.9% had less than four years of schooling, 32.7% had
four to seven, and 15.4% had more than seven. Schooling in those originally
from the State of São Paulo was 37.2%, 43.0% and 19.8%, respectively;
and in those born in other Brazilian states was 63.6%, 26.1% and 10.2% (p<0.005),
respectively.

The proportion
of married individuals (38.2%; 140/377) was lower than that of single, widowed,
divorced and those with no steady partners (61.8%; 233/377) (p<0.001).

Overall TB mortality
rate was 5.1 per 100,000 inhabitants per year, 8.3 in men and 2.3 in women,
and increasing with age (Figure 1). Mortality
rates in those originally from the State of São Paulo, in the south and
central-west regions and in a combination of the north, northeast, and southeast
regions, excluding the State of São Paulo, were 2.5, 3.7 and 6.1 per
100,000 inhabitants per year, respectively. Taking the former as reference,
relative risks were 1.48 (95% CI: 0.79;2.66) and 2.48 (95% CI: 1.98;3.01), respectively.

There were no deaths
reported in 8/96 (8.3%) districts of the city, whereas in 11/96 (11.5%) mortality
rates were equal to or higher than twice the mean rates in São Paulo,
reaching as high as 34.3 per 100,000 inhabitants per year. Figure
2 illustrates the distribution of mortality rates and HDI per district.
The percent distribution of deaths shows that 2.6%, 52.2%, 34.6% and 4.1% lived
in districts with HDI below 0.40, 0.40 to 0.50, 0.51 to 0.69 and above 0.69,
respectively.

When those who
were untreated or treated for up to one week were classified as not effectively
treated, no significant differences were found between treated and untreated
patients by gender, age, marital status, schooling and ethnicity (p>0.05)
(Table 1).

After a similar
comparison was carried out for diabetes, cancer, chronic obstructive pulmonary
disease, HIV co-infection, pulmonary symptoms at the time of diagnosis, weight
loss, smoking and alcohol abuse, it was evidenced that untreated patients were
more likely to have HIV infection (p<0.005) and history of alcohol abuse
(p<0.01) (Table 2).

DISCUSSION

A decline in TB
mortality has been seen in the city of São Paulo since 1996, which could
be in part attributed to the introduction of new antiretroviral therapies. These
treatments have reverted the growing trends started from mid-80s due to the
impact of TB-HIV co-infection.1,2 Despite this mitigation, TB has
remained a major cause of death in the city, affecting mostly those living in
lower HDI districts, evidencing a strong impact of socioeconomic factors, as
seen in other Brazilian capitals.14

Yet, the data found
in the present study reveal only part of the problem. If TB deaths as an associated
cause were also included, the observed magnitude would be dramatically greater.17
In addition, the results are likely to be underestimated since the number of
deaths among those people presumably homeless was relatively low based on social
indicators of the city of São Paulo.e
On the other hand, no reporting of deaths among patients originally from other
Latin American countries contrasts with the current growing migration flows
from areas with high TB prevalence.16

A close examination
of the characteristics of patients progressing to death revealed that mortality
rates by gender and age groups found in the present study were corroborated
in the literature.14,17,20 Higher TB risk seen among the elderly
was probably due their lower immunity, more difficult diagnosis of TB as well
as to the fact that older cohorts were more exposed to infection in the past.22

Higher TB death
rates found among migrants from other Brazilian regions may be because they
are usually older,2,5 belong to the poorest segments of society and
come from areas with high TB prevalence.3

High TB prevalence
among patients with diabetes, chronic obstructive pulmonary disease, smokers
and those with past history of alcohol abuse suggest that biological, socioeconomic,
and behavioral factors played a role in increasing their vulnerability and favored
TB progressing to more severe forms and death.3,5,12,22

The prevalence
of TB-HIV co-infection found in the study is lower than that reported in studies
conducted in 1990s,2,20 but similar to Oliveira et al15
recent findings of reduced mortality in TB-HIV co-infected people probably due
to the introduction of new highly active antiretroviral therapy.

The high proportion
of cases diagnosed after death or untreated, treated for less than a month and
progressing to death right after hospital admission make clear the failure of
health services to identify and timely treat a substantial number of TB patients
in the city of São Paulo. These characteristics make these cases potentially
preventable and they should be a priority in targeted public health interventions.

Allied to that,
the predominance of bacillary forms and the small proportion of cases identified
in primary care services and of those receiving home visit to improve treatment
compliance scale up the risk of disease transmission among those exposed, reducing
or neutralizing the impact of TB control activities.8,11 Similarly
to that seen in other Brazilian regions,20 about half of TB deaths
were underreported cases and thus gone unidentified by TB Control Program before
their deaths.

Low schooling of
patients progressing to death may have contributed to their inability to perceive
the disease. But a recent study in a Brazilian capital city did not show any
association between difficult access to health services and delay in TB diagnosis
and treatment.18 This finding is consistent with free and universal
access to TB diagnosis and treatment in Brazil and broad coverage provided in
primary care services in the city of São Paulo.

Since a large proportion
of patients here studied showed TB typical signs and symptoms, it suggests that
health providers failed to suspect TB in high-risk groups or in those with clinical
presentations indicative of infection.

The high proportion
of patients with past history of TB in the two years prior to their death and
treatment default, and the fact that some of them have been treated with 1R
regimen (isoniazid, rifampicin, pyrazinamide, and ethambutol) allow to assuming
that, at least, part of these deaths may be associated to multidrug-resistant
Mycobacterium tuberculosis.5,21 In addition, it suggests inadequate
follow-up of patients and their close contacts during treatment and for at least
two years after treatment.

The high prevalence
of patients infected with Mycobacterium tuberculosis hinders a significant
decline in TB rates in the short run in Brazil. However, the study findings
indicate that widely implementing the Directly Observed Therapy Short-Course
(DOTS) strategy and prioritizing migrant population, districts with the lowest
HDI as well as targeting those at higher risk of progressing to severe disease
will favor a rapidly reduction of TB mortality as achieved by other countries
where TB was also a serious public health concern.6,7,19

Hence, it would
be advisable to change the DOTS strategy in São Paulo since it has aimed
at providing universal coverage to TB patients but lacks a special focus on
high-risk groups for TB death. On the other hand, there is a need for further
studies to better understanding TB death predictors in the Brazilian scenario.
From an operational perspective, given Brazil's large population size, huge
poverty-stricken areas and high incidence rates of TB, it is crucial to provide
adequate infrastructure for diagnosis which could facilitate systematic search
of TB cases among patients with respiratory symptoms seeking care at primary
health units.